1. Field of the Invention
The invention relates to the processing of protein-containing fluids obtained from the body.
In many medical and surgical procedures, protein-containing fluids are drained from the body as a treatment of the body. In general, however, the loss of the protein in the fluid is disadvantageous, because it produces unwanted side-effects. It has been proposed, in some cases, to return the drained fluid to the body, often after filtration and/or other cleansing (e.g. immunoabsorbance), but in general this has not proved entirely satisfactory because of an adverse reaction by the body to the components within the returned fluid.
For example, ascites is the abnormal accumulation of protein-containing fluid in the peritoneal cavity and is frequently encountered in patients with cirrhosis and other forms of severe liver disease. It may also arise in cases of cardiac and renal disease.
2. Brief Review of the Prior Art
Ascites is commonly treated with bed rest, salt restriction and drugs that increase sodium excretion and/or urine output. Drainage of ascitic fluid (paracentesis) may be performed, particularly in cases of advanced cirrhosis when the ascites does not respond to medical intervention.
The ascitic fluid may, in such paracentesis, be drained into the superior vena cava via a surgically implanted peritoneovenous shunt including a one-way valve. Such shunts are, however, associated with a high rate of complications including infection, disseminated intravascular coagulation and thrombosis of the shunt.
In general, therefore, such shunts are avoided and the ascitic fluid is drained out of the patient by paracentesis. Such paracentesis, particularly at large volumes, is associated with hypovolaemia, uraemia and electrolyte disorders since this results in the simultaneous loss of proteins promoting a low protein level. It has been found that these disorders are generally preventable by the simultaneous intravenous infusion of protein in the form of albumen solutions. As indicated in the review by McCormick P. A. and Mcintyre N., [Brit J Hosp Med 47(10): 738-744 (1992)], large volume paracentesis with intravenous colloid infusion is more effective in treating ascites than the standard diuretic therapy with fewer complications and reduced hospital stay.
The use of albumen infusions together with large volume paracentesis has disadvantages. Commercially available albumen is currently largely derived from human plasma with associated high costs, limited availability and the potential untoward effects of infusing blood products. In some countries albumen is poorly available.
A number of studies have described the intravenous infusion of drained ascitic fluid after a variety of processes to remove unwanted substances including excess water.
Bruno et al, [British Medical Journal 304: 1655-1688 (1992)] describe paracentesis by drainage from the peritoneal cavity by gravity into a hemofilter of polyamide fibre (FH88, Gambro, Lund, Sweden) with an effective surface area of 2 m.sup.2. The filter filters and concentrates the ascitic fluid separating protein from the water and solutes forming the filtrate. The concentrated ascites is periodically returned to the peritoneal cavity under gravity so that the cavity serves as a mixing chamber for a progressively concentrated ascitic fluid. The concentrate obtained after the last passage is then reinfused through a catheter inserted into an ante-cubital vein. The filtrate (water and electrolytes) is discarded.
Bruno et al note some cases of fever associated with this procedure and suggest that they are self-limiting. However, Katoh S. et al, [Jpn J Med 30(4) 311-317 (1991)] identify fever as a major problem associated with the intravenous reinfusion of ascites after filtration and concentration and state that the incidence of fever sometimes necessitates the cessation of the reinfusion procedure. Katoh et al suggest that the usefulness of reinfusion of ascites would be increased if this adverse reaction could be overcome.
Katoh et al identify microaggregates, including fibrin, remaining in ascites after filtration and concentration as a cause of such fever. They propose their removal by the use of one of two different types of 40 .mu.m microfilters--either screen filters or depth filters. As a screen filter, Katoh et al use a pleated woven polyester filter having an area of 160 cm.sup.2 with a rating of 40 .mu.m and a priming volume of 20 ml. As a depth filter, Katoh et al use a nylon filter with a rating of 0.8 .mu.m and a priming volume of 20 ml.
Katoh et al find little or no reduction of fever by the use of the depth filter but some, although not a total, reduction in fever using a screen filter. Katoh et al thus conclude that some other substance or substances present in the ascites are responsible for the fever. They discuss a number of pyrogenic substances including endotoxins, collagens and cytotoxic polypeptides but fail to locate the substance inducing the febrile reaction.
Fever is also noted as a side effect of intravenous infusion of ascites by Inaba T. et al [J Jpn Soc Dial Ther 24(2): 143-149 (1991)]. This paper refers to the use of screen filters and antipyretics to reduce the incidence of such fever. It also discusses the addition of anti-cancer agents prior to the re-introduction of the filtered ascitic fluid into patients with malignant tumours.
Fibrin is also discussed as a cause of fever and the use of a screen filter to reduce its incidence is mentioned by Andoh T. et al, [Jpn J Haemodial 20(12): 931-936 (1987)].